rTMS May Alleviate Common, Resistant Schizophrenia Symptoms

Repetitive transcranial magnetic stimulation (rTMS) is both safe and effective for treating nonexistent spoken voices heard by patients with schizophrenia, new research showed.

In a randomized, sham controlled trial, patients who received imaging-navigated active rTMS over the left temporoparietal junction had a significantly greater reduction in Auditory Hallucination Rating Scale (AHRS) scores at both 2 and 6 weeks than those who received sham rTMS, meeting its primary outcome.

In addition, those receiving the active treatment showed significant improvement in both positive and negative symptoms on the Positive and Negative Syndrome Scale (PANSS). This suggests “our TMS protocol may be generalized to other symptoms of schizophrenia,” corresponding author Gong-Jun Ji, PhD, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China, told Medscape Medical News.

Ji added that the number-one takeaway message for clinicians is the importance of the precise localization of the TMS coil. “You need the patient’s brain structural images and a navigation system to ensure that your TMS coil aligned with the cortical target during the treatment,” he said.

There were no treatment-related serious adverse events reported for any of the study participants.

The findings were published online on November 11 in JAMA Network Open.

Persistent, Drug-Resistant Symptom

Ji noted that their Brain Imaging and Neuromodulation lab aims to resolve clinical problems of neurology and psychiatric disorders — and that auditory hallucination has been a persistent drug-resistant symptom that severely affects a patient’s daily life.

In fact, the investigators noted that this symptom occurs in about 70%-80% of patients with schizophrenia, with 25%-30% not responsive to antipsychotic medications.

Ji added that although TMS has previously shown potential, its efficacy was still “undetermined.”

The current double-blind trial was conducted from September 2016 through August 2021 and included 62 adult participants (mean age, 27.4 years; 53% women) who completed 2 weeks of treatment. All had schizophrenia and were experiencing auditory verbal hallucinations.

Of these, 32 were randomly assigned to receive three daily sessions of active rTMS for 2 weeks, and the other 30 received matching sham treatment. Both groups underwent structural and resting-state functional MRI at baseline before start of study treatment.

The rTMS protocol used a transcranial magnetic stimulator with a 70-mm air-cooled figure-of-eight coil. In the other group, a sham coil was used that was identical in appearance and sound and generated sensations to the scalp but no current.

While improvements in auditory hallucinations between baseline and week 2 and week 6 was the primary outcome measure, secondary outcome measures included TMS-induced electric field strength, using baseline structural brain images; scores on the PANSS; and response to rTMS, defined as a 25% or greater reduction in AHRS score from baseline to week 2 and week 6.

Practice-Changing?

Results showed significantly greater reductions in AHRS scores for the active rTMS group than for the sham treatment group at week 2 (difference, 5.96; 95% CI, 3.4-8.5; P P

Higher response rates were also found for the active vs sham groups at week 2 (47% vs 13%; P = .004; odds ratio [OR], 5.74) and at week 6 (50% vs 6%; P = .002; OR, 17).

In addition, there were significant greater changes for active vs inactive rTMS at week 2 and week 6 in PANSS total (P P = .001), and negative (P

Greater reductions in AHRS scores were also significantly linked to a stronger TMS-induced electric field (P = .002), and the strength of this field “was independently associated with symptom improvements,” the investigators reported.

This suggests “that the electric field strength in the individualized [auditory verbal hallucination] network is a vital perimeter for optimizing the efficacy of the rTMS protocol,” they added.

Overall, the study “provides strong evidence that precise rTMS can alleviate hallucination symptoms” in patients with schizophrenia, co-corresponding author Kai Wang, MD, Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China, told Medscape Medical News.

“I would suggest clinicians combine the rTMS and medication at the beginning of treatment, before patients are drug-resistant,” Wang added.

He said his team is currently planning a multicenter, randomized controlled study to further validate the current findings, and that there’s a possibility that they may also compare efficacy between precise rTMS and conventional 10-20 system-guided rTMS.

‘Intriguing First Step’

Commenting for Medscape Medical News, Anil K. Malhotra, MD, director of the Institute of Behavioral Science at the Feinstein Institutes for Medical Research at Northwell Health, Manhasset, New York, called the research “pretty intriguing” and noted that there have been very few studies of TMS in schizophrenia in general.

“This was a pretty focused investigation using a relatively novel technique in terms of image-guided TMS, and the results looked relatively strong,” said Malhotra, who was not involved with the research.

However, he noted that “it would have been nice” if the treatment duration had been a bit longer than 2 weeks. “For most TMS work that we do and others do, one usually goes to 4 weeks. So it’s a little hard to compare and contrast with other studies,” he added.

He reported that his investigative team is currently in the middle of a study assessing TMS for social cognition in schizophrenia.

“That’s the other thing I would have liked to have seen. There’s no data on cognition in the study from China,” Malhotra said. He added that although their study targeted a different part of the brain than his study is targeting, “it still would have been of interest to see if there was some specific effect from some neurocognitive measure that we’re perhaps not measuring. And we might have added that measure to our study.”

Overall, Malhotra said that because this was a relatively small study conducted only in one country, “I wouldn’t use this paper as a rationale for a new clinical treatment strategy. Larger-scale studies in different populations will be necessary before we actually change clinical practice.”

That said, he added that he believes this is “a very intriguing first step.”

The study was funded by a number of grants, including from the National Natural Science Foundation of China, the Science Fund for Distinguished Young Scholars of Anhui Province, and the Collaborative Innovation Project Between Universities and the Hefei Comprehensive National Science Center. The investigators reported no relevant financial relationships. Malhotra also reported having no relevant financial relationships, but did note his involvement with an ongoing study on TMS for social cognition in schizophrenia.